Prognosis-related VDAC1 regulates the proliferation and apoptosis of osteosarcoma cells via the MAPK signaling pathway.

The role of VDAC1 in osteosarcoma is unclear. We explored the effect of VDAC1 on osteosarcoma development by combining bioinformatic analysis and experimental identification. This study suggested that VDAC1 is an independent prognostic factor for osteosarcoma. Patients with high VDAC1 expression have a poor survival rate. VDAC1 was overexpressed in osteosarcoma cells. After silencing VDAC1, the proliferation of osteosarcoma cells decreased, and the apoptosis rate increased. Gene set variation analysis and gene set enrichment analysis indicated that VDAC1 was associated with the MAPK signaling pathway. After VDAC1 siRNA, SB203580 (a p38 inhibitor), SP600125 (a JNK inhibitor) and α-pifithrin (a p53 inhibitor) treatment, the proliferative capacity was weaker in the si-VDAC1 group than in the si-VDAC1 + SB203580, si-VDAC1 + SP600125, and si-VDAC1 + α-pifithrin groups. In conclusion, prognosis-related VDAC1 can affect osteosarcoma cells' proliferative activity and apoptosis level. The MAPK signaling pathway mediates VDAC1 regulation of osteosarcoma cell development.

Transcriptome-wide association study-derived genes as potential visceral adipose tissue-specific targets for type 2 diabetes.

AIMS/HYPOTHESIS: This study aimed to assess the causal relationship between visceral obesity and type 2 diabetes and subsequently to screen visceral adipose tissue (VAT)-specific targets for type 2 diabetes. METHODS: We examined the causal relationship between VAT and type 2 diabetes using bidirectional Mendelian randomisation (MR) followed by multivariable MR. We conducted a transcriptome-wide association study (TWAS) leveraging prediction models and a large-scale type 2 diabetes genome-wide association study (74,124 cases and 824,006 controls) to identify candidate genes in VAT and used summary-data-based MR (SMR) and co-localisation analysis to map causal genes. We performed enrichment and single-cell RNA-seq analyses to determine the cell-specific localisation of the TWAS-identified genes. We also conducted knockdown experiments in 3T3-L1 pre-adipocytes. RESULTS: MR analyses showed a causal relationship between genetically increased VAT mass and type 2 diabetes (inverse-variance weighted OR 2.48 [95% CI 2.21, 2.79]). Ten VAT-specific candidate genes were associated with type 2 diabetes after Bonferroni correction, including five causal genes supported by SMR and co-localisation: PABPC4 (1p34.3); CCNE2 (8q22.1); HAUS6 (9p22.1); CWF19L1 (10q24.31); and CCDC92 (12q24.31). Combined with enrichment analyses, clarifying cell-type specificity with single-cell RNA-seq data indicated that most TWAS-identified candidate genes appear more likely to be associated with adipocytes in VAT. Knockdown experiments suggested that Pabpc4 likely contributes to regulating differentiation and energy metabolism in 3T3-L1 adipocytes. CONCLUSIONS/INTERPRETATION: Our findings provide new insights into the genetic basis and biological processes of the association between VAT accumulation and type 2 diabetes and warrant investigation through further functional studies to validate these VAT-specific candidate genes.

The Dawn of a New Era: Tumor-Targeting Boron Agents for Neutron Capture Therapy.

Cancer is widely recognized as one of the most devastating diseases, necessitating the development of intelligent diagnostic techniques, targeted treatments, and early prognosis evaluation to ensure effective and personalized therapy. Conventional treatments, unfortunately, suffer from limitations and an increased risk of severe complications. In light of these challenges, boron neutron capture therapy (BNCT) has emerged as a promising approach for cancer treatment with unprecedented precision to selectively eliminate tumor cells. The distinctive and promising characteristics of BNCT hold the potential to revolutionize the field of oncology. However, the clinical application and advancement of BNCT technology face significant hindrance due to the inherent flaws and limited availability of current clinical drugs, which pose substantial obstacles to the practical implementation and continued progress of BNCT. Consequently, there is an urgent need to develop efficient boron agents with higher boron content and specific tumor-targeting properties. Researchers aim to address this need by integrating tumor-targeting strategies with BNCT, with the ultimate goal of establishing BNCT as an effective, readily available, and cutting-edge treatment modality for cancer. This review delves into the recent advancements in integrating tumor-targeting strategies with BNCT, focusing on the progress made in developing boron agents specifically designed for BNCT. By exploring the current state of BNCT and emphasizing the prospects of tumor-targeting boron agents, this review provides a comprehensive overview of the advancements in BNCT and highlights its potential as a transformative treatment option for cancer.

Basic performance of domestic surgical robot and the safety and effectiveness of integrated energy equipment. / å›½äº§æ‰‹æœ¯æœºå™¨äººåŸºæœ¬æ€§èƒ½å’Œæ•´åˆèƒ½é‡è®¾å¤‡çš„å®‰å ¨æ€§åŠæœ‰æ•ˆæ€§.

OBJECTIVES: Surgical robot system has broken the limitation of traditional surgery and shown excellent performance in surgery, and has been widely used in minimally invasive treatment in most areas of surgery. This study aims to verify the basic performance of the domestic surgical robot system and the safety and effectiveness of the integrated bipolar electrocoagulation and ultrasonic knife. METHODS: The basic performance of the domestic surgical robot system was evaluated by completing the square knot and surgical knot, vertical and horizontal perforation and right ring perforation and suture, as well as picking up beans. Compared with laparoscopy, the safety and effectiveness of the domestic surgical robot after integrated interconnection bipolar electrocoagulation and ultrasonic scalpel were evaluated by detecting the vascular closure performance and the degree of histopathological damage in animals. RESULTS: Compared with freehand knotting, domestic robot knotting speed and circumference were slightly worse, but better than laparoscopic knotting. There was no statistical significance in the tension difference of the surgical knots among the 3 methods (P>0.05), but the tension of the square knots made by the freehand and the domestic surgical robot was greater than that of the laparoscopy (P<0.05). The space required for both the left and right forceps heads of knots was smaller than that of laparoscopy (P<0.001), which successfully completed the 4 quadrant suture tasks, and the time of picking up beans was significantly less than that of laparoscopy (P<0.05). There was no significant difference in the temperature of the liver tissue after the bipolar electrocoagulation between the interconnected domestic surgical robot and the laparoscopy (P>0.05), and the acute thermal injury was observed under the light microscope. The temperature of the liver tissue treated by the domestic robotic ultrasound knife was higher than that of the laparoscopic ultrasound knife (P<0.05). CONCLUSIONS: Domestic surgical robots are obviously superior to laparoscopy in suturing, knotting, and moving objects, and domestic surgical robots' interconnect bipolar electrocoagulation and ultrasonic knife have achieved success in animal experiments, and hemostasis is considered to be safe and effective.

Liquid biopsy at the frontier of detection, prognosis and progression monitoring in colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of carcinogenic death. To date, surgical resection is regarded as the gold standard by the operator for clinical decisions. Because conventional tissue biopsy is invasive and only a small sample can sometimes be obtained, it is unable to represent the heterogeneity of tumor or dynamically monitor tumor progression. Therefore, there is an urgent need to find a new minimally invasive or noninvasive diagnostic strategy to detect CRC at an early stage and monitor CRC recurrence. Over the past years, a new diagnostic concept called "liquid biopsy" has gained much attention. Liquid biopsy is noninvasive, allowing repeated analysis and real-time monitoring of tumor recurrence, metastasis or therapeutic responses. With the advanced development of new molecular techniques in CRC, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and tumor-educated platelet (TEP) detection have achieved interesting and inspiring results as the most prominent liquid biopsy markers. In this review, we focused on some clinical applications of CTCs, ctDNA, exosomes and TEPs and discuss promising future applications to solve unmet clinical needs in CRC patients.

The impact of robotic technology on the learning curve for robot-assisted gastrectomy in the initial clinical application stage.

OBJECTIVE: To evaluate the impact of robotic technology on the learning curve for robot-assisted gastrectomy in the initial clinical application stage and to compare RAG with laparoscopic-assisted gastrectomy using a short-term evaluation. METHODS: Between September 2016 and December 2018, 111 consecutive distal gastric cancer patients who were candidates for RAG or LAG were prospectively enrolled. Operative findings, morbidity, oncological findings, and the learning curve were analyzed. RESULTS: Thirty patients underwent RAG with the da Vinci Si robot system, and eighty-one patients underwent LAG. Blood loss was lower during RAG than during LAG (133.80 ± 95.28 vs. 178.83 ± 98.37, P = 0.046). The operative time for RAG was significantly longer (304.45 ± 42.08 vs. 281.17 ± 32.69, P = 0.015). The number of retrieved lymph nodes (LNs) was greater (37.33 ± 8.25 vs. 32.78 ± 5.98, P = 0.003) with RAG. Notably, RAG had an advantage in the dissection of No. 9 and 11p LNs (3.56 ± 1.76 vs. 2.78 ± 1.30, P = 0.038; 2.48 ± 0.93 vs. 1.99 ± 0.84, P = 0.015, respectively). Severe complications were less frequent in the RAG group (7 (8.6%) vs. 1 (3.3%), P = 0.003). No significant differences in terms of postoperative recovery were found between the two groups. The learning curve for RAG showed that the cumulative sum value decreased from the 10th case, while it decreased from the 28th case in the LAG group. CONCLUSION: By means of robotic technology, RAG is better than LAG for the dissection of No. 9 and 11p LNs and for the alleviation of surgical trauma, and the technique is learned more rapidly during the preliminary stage than the LAG technique.

Micro-Hand Robot-Assisted Versus da Vinci Robot-Assisted Cholecystectomy: A Multi-centre, Randomized Controlled Trial.

OBJECTIVE: To evaluate the clinical effectiveness of micro-hand robot-assisted cholecystectomy (MRC) by comparing the clinical outcomes of patients with benign gallbladder disease treated with micro-hand or da Vinci robot-assisted cholecystectomy (DRC). METHODS: This is a prospective, multi-centre, single-blind, and randomized controlled trial. In this study, 166 patients of benign gallbladder disease were randomized enrolled into two groups and received MRC or DRC (83 in the MRC group; 83 in the DRC group). The primary endpoint was surgical success rate. Secondary endpoints were the docking time, console time, total operation time, intraoperative blood loss, gallbladder breakage rate, postoperative pain, time of first flatus, the comprehensive complication index (CCI), and the hospital stay of the subjects. The duration of follow-up was 30 days. RESULTS: No conversion occurred. Compared with MRC, the DRC group showed longer docking time (12.04 min vs. 16.39 min, P = 0.025) and higher gallbladder breach rate (4.8% vs. 15.7%, P = 0.021). The MRC group showed higher postoperative pain scores compared to DRC (4.0 vs 3.0, P = 0.038). The console time, intraoperative blood loss, and gallbladder breach rate were comparable in these two groups (P > 0.05). No differences were observed in postoperative outcomes and complications between the two groups (P > 0.05). CONCLUSIONS: In patients with benign gallbladder disease, the MRC showed no obvious clinical disadvantage compared with the da Vinci surgical robot. MRC is effective and safe and provides more options for surgical treatment. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov (NCT04122261). URL: https://clinicaltrials.gov/ct2/show/NCT04122261.

Diagnostic accuracy of the visceral adiposity index in patients with metabolic-associated fatty liver disease: a meta-analysis.

BACKGROUND: Conflicting results on the prognostic value of the visceral adiposity index (VAI) in patients with metabolic-associated fatty liver disease (MAFLD) have been reported. This study aimed to assess the diagnostic value of the VAI in MAFLD patients. METHODS: The Cochrane Library, PubMed, Embase, and other databases were searched to collect all documents that met the inclusion criteria from the establishment of the database to September 2021. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. The heterogeneity among the studies was analysed by the Cochran Q test and I2 test, and the appropriate model was selected according to the heterogeneity results. The diagnostic efficacy of the VAI was evaluated by sensitivity, specificity, and area under the curve, and a Fagan diagram was generated to evaluate the diagnostic ability of the VAI. RESULTS: A total of 9 studies were included. The overall quality of the included studies was good. Meta-analysis showed that the combined sensitivity of the VAI for the diagnosis of MAFLD was 0.70 [95% CI (0.69-0.71)], the combined specificity was 0.67 [95% CI (0.67-0.68)], the combined positive likelihood ratio was 2.08 [95% CI (1.87-2.31)], the combined negative likelihood ratio was 0.39 [95% CI (0.34-0.44)], and the combined diagnostic odds ratio was 5.81 [95% CI (4.73-7.14)]. The corresponding area under the curve was 0.79 [95% CI (0.75-0.82)]. Meta-regression analysis showed that the diagnostic method was a potential source of heterogeneity (P < 0.05). The Fagan diagram showed that the precision of MAFLD diagnosis was 70% when the pretest probability was set to 50% and then supplemented by the VAI. CONCLUSIONS: The VAI is an independent predictor in the diagnosis of MAFLD and may be helpful in the detection of MAFLD. A VAI > 2.33 suggests that patients have a high probability of having MAFLD.

Revisional large gastric pouch with Roux-en-Y gastric bypass for patients with type 2 diabetes and a body mass index less than 35 kg/m2: a cause and effect analysis.

PURPOSE: To evaluate the long-term efficacy of large gastric pouch surgery and revisional surgery in patients with a body mass index (BMI) < 35 kg/m2 and type 2 diabetes mellitus (T2DM). METHODS: We conducted a retrospective review of patients who underwent laparoscopic Roux-en-Y gastrojejunostomy with a large gastric pouch in our hospital. The clinical pre- and post-surgery data, including BMI, waist circumference, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipid metabolism-related indicators, homoeostatic model assessment of insulin resistance (HOMA-IR), and major complications, were recorded and analyzed. RESULTS: Twenty-four patients were included in the analysis, 12 of whom underwent revisional surgery. At their 5-year-follow-up after the primary surgery, the BMI and waist circumference of the patients with T2DM were lower than their baseline values. The BMI, HbA1c, HOMA-IR, FPG and waist circumference also decreased after the revisional surgery. The rates of remission of diabetes after the primary vs. after the revisional surgery were 4.17% vs. 41.70%, respectively (P < 0.05). CONCLUSION: Roux-en-Y gastrojejunostomy with a large gastric pouch is not effective in the long term and, therefore, is unsuitable for Chinese patients with T2DM and a BMI < 35 kg/m2. Conversely, revisional surgery has a definite effect on these patients.

Comparison of the short-term efficacy of two types of robotic total mesorectal excision for rectal cancer.

BACKGROUND: The advantages and disadvantages of robotic technology compared with conventional surgery for low rectal cancer have been discussed extensively. However, a few studies on the efficacy of total mesorectal excision (TME) with different robotic technologies have been reported. The aim of this study was to evaluate the efficacy of two types of robot-assisted TME (R-TME) compared with laparoscopic TME (L-TME). METHODS: A prospective comparative study was conducted comparing da Vinci R-TME, Micro Hand S R-TME, and L-TME for rectal cancer. This study was registered with "Clinicaltrials.gov" (ID: NCT02752698) and approved by the Association for the Accreditation of Human Research Protection Program (AAHRPP) (Project number: T16007). Between January 2017 and May 2019, patients with rectal cancer (cT1-3NxM0) were prospectively registered in the Third Xiangya Hospital. The integrity of the TME sample served as the primary outcome. Secondary outcomes included the involvement of the circumferential and distal resection margins (CRM and DRM), number of lymph nodes retrieved, blood loss, operative time, conversion rate, comprehensive complication index score, the International Prostate Symptom score, the International Index of Erectile Function, and the Female Sexual Function Index. RESULTS: Of 134 patients with rectal cancer (74 males, mean age [SD] 59.1 ± 8.27 years), 46 patients underwent laparoscopic TME, 45 patients underwent da Vinci R-TME, and 43 patients underwent Micro Hand S R-TME. There were no differences in results between the two types of R-TME. Compared with laparoscopic TME, significant reductions in blood loss (median 65.50 ml da Vinci; median 66.54 ml Micro Hand S vs median 95.04 ml L-TME p = 0.037 and p = 0.041, respectively) and conversion rate (2.2% da Vinci; 2.3% Micro Hand S vs 6.8% L-TME p = 0,040 for the comparison daVinci L-TME and p = 0.038 for the comparison Micro Hand S vs. L-TME) with da Vinci Si and Micro Hand S R-TME were noted, and significant increases in operation time (230.05 min da Vinci; 235.03 min Micro Hand S vs. 205.53 min L-TME p = 0.045 and p = 0.043, respectively) was observed. Additionally, more patients underwent TME with sphincter-preserving methods in the two R-TME groups based on the type of operation (da Vinci 97.7%; Micro Hand S 97.9% vs. L-TME 82% resulting in  p = 0.033 for the comparison daVinci L-TME and p = 0.035 for the comparison Micro Hand S vs. L-TME). In comparison with L-TME, there was a larger number of lymph nodes retrieved (da Vinci mean 17.54; Micro Hand S mean 17.32 vs. L-TME mean 14.96 p = 0.031 for the comparison daVinci L-TME and p = 0.033 for the comparison Micro Hand S vs L-TME) and less blood loss (da Vinci mean 65.50 ml; Micro Hand S mean 66.54 ml vs. L-TME mean 95.04 ml, p = 0.037 for the comparison daVinci L-TME and p = 0.041 for the comparison Micro Hand S vs. L-TME), and incidence of severe postoperative complications was similar among three TME groups except for the earlier recovery of urogenital function (mean IPSS score da Vinci 7.73±1.35; Micro Hand S7.75±1.47 vs L-TME 14.26±1.41 p<0.001 for the comparison da Vinci L-TME and p<0.001 for the comparison Microhand S vs L-TME) in the two R-TME groups. CONCLUSIONS: In our study, compared with laparoscopic surgery, da Vinci or Micro Hand R-TME exhibited similar superiority in the quality of oncologic resection, postoperative morbidity, and recovery of postoperative function.

TyG Index Performs Better Than HOMA-IR in Chinese Type 2 Diabetes Mellitus with a BMI < 35 kg/m2: A Hyperglycemic Clamp Validated Study

Background and objectives: Chinese type 2 diabetes mellitus (T2DM) patients are characterized by a low body mass index (BMI), and significant insulin resistance (IR). The triglyceride glucose (TyG) index has not been studied as a means of assessing IR in Chinese T2DM patients with a BMI < 35 kg/m2. Materials and Methods: An open-label cross-sectional study recruited 102 Chinese T2DM patients with a BMI < 35 kg/m2. The hyper-insulinemic euglycemic clamp, homeostatic model assessment of IR (HOMA-IR), and TyG index were used to determine the level of IR. Based on Pearson's correlations, glucose disposal rate (GDR), TyG index, and HOMA-IR were analyzed. HOMA-IR and TyG index for IR were evaluated using multiple linear regression and multivariate logistic regression analyses. On the basis of the receiver operating characteristic (ROC) curve, the sensitivity, specificity, and optimal cut-off value of HOMA-IR and the TyG index were determined. Results: The mean values of GDR, HOMA-IR, and TyG index were 4.25 ± 1.81, 8.05 ± 7.98, and 8.12 ± 0.86 mg/kg/min, respectively. Pearson's correlation coefficient was −0.418 between GDR and TyG index and −0.324 between GDR and HOMA-IR. ROC curve analysis showed that, among both sexes, the TyG index was a better discriminator of IR than HOMA-IR. The area under the ROC curve (AUC) of the TyG index (0.785, 0.691−0.879) was higher than that of HOMA-IR (0.73, 0.588−0.873) in all genders. The optimal cut-off values of the TyG index and HOMA-IR were 7.99 and 3.39, respectively. Conclusions: The TyG index showed more effectiveness in identifying IR in Chinese T2DM patients with a BMI < 35 kg/m2 compared to HOMA-IR.

Comparison of the operative outcomes and learning curves between laparoscopic and "Micro Hand S" robot-assisted total mesorectal excision for rectal cancer: a retrospective study.

BACKGROUND: The Micro Hand S robot is a new surgical tool that has been applied to total mesorectal excision (TME) surgery for rectal cancer in our center. In this study, we compared the operative outcomes, functional outcomes and learning curves of the Micro Hand S robot-assisted TME (RTME) with laparoscopic TME (LTME). METHODS: A total of 40 patients who underwent RTME and 65 who underwent LTME performed by a single surgeon between July 2015 and November 2018 were included in this retrospective study. Clinicopathologic characteristics, operative and functional outcomes, and learning curves were compared between the two groups. The learning curve was analyzed using the cumulative sum method and two stages (Phase 1, Phase 2) were identified and analyzed. All patients were followed up for at least 12 months. RESULTS: The clinicopathologic characteristics of the two groups were similar. The learning curve was 17 cases for RTME and 34 cases for LTME. Compared with LTME, RTME was associated with less blood loss (148.2 vs. 195.0 ml, p = 0.022), and shorter length of hospital stay (9.5 vs. 12.2 days, p = 0.017), even during the learning period. With the accumulation of experience, the operative time decreased significantly from Phase 1 to Phase 2 (RTME, 360.6 vs. 323.5 min, p = 0.009; LTME, 338.1 vs. 301.9 min, p = 0.005), whereas other outcomes did not differ significantly. CONCLUSIONS: Micro Hand S robot-assisted TME is safe and feasible even during the learning period, with outcomes comparable to laparoscopic surgery but superior in terms of blood loss, length of hospital stay, and learning curve. Trial registration Clinicaltrial.gov, NCT04836741, retrospectively registered on 5 April 2021.

Robot-assisted sleeve gastrectomy in patients with obesity with a novel Chinese domestic MicroHand SII surgical system.

BACKGROUND: A new device has been added to the Chinese MicroHand surgical robot family, developed based on the successful application of control algorithms. As a benefit of using these specialized control algorithms, the motion mapping relation can be accommodated into the system without the help of a built-in image system, resulting in a novel Chinese domestic surgical robot with two arms called MicroHand SII, which is different from the former MicroHand S and da Vinci systems. In this study, we investigate the performance of a novel MicroHand SII robotic platform in patients with obesity. METHODS: From March 2018 to April 2019, a total of 7 patients whose BMI ranged from 29.9 to 49.8 kg/m2 were operated on with the robot-assisted technique using the MicroHand SII surgical system. Data regarding demography, surgical procedure and the 3-month outcome postoperation were collected. RESULTS: There were 2 female and 5 male patients with a median age (range) of 35 (20-51) years. The median operative time was 160 (149-195) minutes. None were converted to open surgery. All anthropometry indices improved significantly (p < 0.05) at 3 months postoperatively. There were no cases of surgical site infection, gastrointestinal/abdominal bleeding, or conversion to an open operation. CONCLUSIONS: The initial experience showed that the Chinese domestic robot surgical system MicroHand SII could be feasibly and safely applied in sleeve gastrectomy in patients with obesity. Because of the unique design of this system such as a two-hand robot, an array of master-slave motion strategies, and a roll joint at the end of the instruments that allows 7 degrees of freedom, this robotic platform has presented its own obvious advantages.

Laparoscopic Roux-en-Y gastric bypass in Type 2 diabetes mellitus patient with low body mass index and gastric stromal tumor: A case report. / 低体重指数2åž‹ç³–å°¿ç— å¹¶èƒƒé—´è´¨ç˜¤æ‚£è€ è ¹è ”é•œä¸‹è¡ŒRoux-en-Y胃旁路术1例.

Laparoscopic Roux-en-Y gastric bypass (LRYGB) has been proved to be a safe and effective treatment for Type 2 diabetes mellitus (T2DM) patients with body mass index (BMI) >27.5 kg/m2 in China. The incidence of gastrointestinal stromal tumor (GIST) is very low, whereas the relevant studies on GIST and LRYGB are few. This is the first report of GIST associated with LRYGB in low BMI Chinese patient with T2DM.A male patient with GIST and T2DM, whose body weight and height were 67 kg and 175 cm, respectively,and the calculated BMI was 21.9 kg/m2. He was diagnosed by gastroscopy and enhanced CT scan. We used LRYGB to treat GIST and T2DM at the same time. After the operation, the GIST was removed successfully. Both the blood glucose levels and glycosylated hemoglobin were normal at 4 months and 1 year later. The patient received follow-up gastroscopy and abdominal CT scan and did not find out local recurrence and metastasis. LRYGB may be the best choice in treating GIST in T2DM with low BMI.

Effect of laparoscopic Roux-en-Y gastric bypass on improvement of insulin resistance in Type 2 diabetic patients evaluated by hyperinsulinemic-euglycemic clamp. / é«˜èƒ°å²›ç´ -正葡萄糖钳夹实验评价Roux-en-Y胃旁路术对2åž‹ç³–å°¿ç— æ‚£è€ èƒ°å²›ç´ æŠµæŠ—çš„æ”¹å–„ä½œç”¨.

OBJECTIVES: With the increase of people's living standards increasing year by year, Type 2 diabetes has brought great economic and living burden to the society and patients. Bariatric surgery can improve metabolic indicators in patients with diabetes, but specific mechanisms are still under study. This study aims to evaluate the effect of Roux-en-Y gastric bypass (RYGB) on insulin resistance in patients with Type 2 diabetes by hyperinsulinemic-euglycemic clamp. METHODS: The peripheral glucose uptake (M value) of 40 patients undergoing laparoscopic Roux-en-Y gastric bypass surgery before and 6 months after the operation were analyzed hyperinsulinemic euglycemic clamp. Fasting blood glucose, glycosylated hemoglobin, triglycerides, andlow-density lipoprotein cholesterol levels as well as body mass index were also analyzed. RESULTS: M value of patients after laparoscopic Roux-en-Y gastric bypass was significantly higher than that before the operation, while indexes such as fasting blood glucose, glycosylated hemoglobin, triglycerides, and low-density lipoprotein cholesterol levels as well as body mass index were lower than those before the operation (all P<0.05). CONCLUSIONS: Laparoscopic Roux-en-Y gastric bypass surgery significantly improves insulin resistance in patients with Type 2 diabetes, decreases blood sugar and blood lipid, and can exert a positive effect on the treatment of Type 2 diabetes.

The MicroHand S robotic-assisted versus Da Vinci robotic-assisted radical resection for patients with sigmoid colon cancer: a single-center retrospective study.

BACKGROUND: Sigmoid colon cancer is a lethal disease and has a strong indication for surgery. Robotic-assisted surgery is one of the promising alternative treatment for this disease. Nowadays, the MicroHand S surgical system and the Da Vinci surgical system have been assembled in China. However, there is still no report to study the therapeutic effects of the two robotic-assisted surgical systems. Thus, the purpose of this study was to compare clinical and economic outcomes of patients with sigmoid colon cancer undergoing robot-assisted radical surgery via The MicroHand S or Da Vinci surgical system. METHODS: The clinical data of 45 patients with sigmoid colon cancer undergoing the MicroHand S or Da Vinci robotic-assisted surgery at The Third Xiangya Hospital of Central South University from January 2017 to January 2019 were retrospectively analyzed. RESULTS: Twenty-one patients received MicroHand S robotic-assisted radical surgery and 24 patients received Da Vinci robot-assisted radical surgery. No significant differences were observed in terms of operation time, number of lymph node harvested, blood loss, intestinal exhaust time, time of oral feeding resumption, volume of abdominal cavity 24-h drainage, hospital stay, complication and rate of conversion, removal time of drainage tube and catheter between MicroHand S and Da Vinci group. However, the MicroHand S group had significantly lower hospitalization costs (P = 0.002) and shorter time to get out of bed after surgery (P = 0.04). In addition, no recurrence and metastases were observed in both groups during the follow-up. CONCLUSIONS: In patients with sigmoid colon cancer, the Da Vinci surgical system did not show obvious clinical advantages compared to the MicroHand S surgical system in surgical outcomes. However, the MicroHand S surgical platform showed advantages in terms of the hospitalization costs and length of postoperative bedtime. The outcome of this study will probably result in a shift to the MicroHand S surgical system as treatment preference in China.

Effect of sleeve gastrectomy on gastroesophageal reflux in patients with metabolic syndrome. / è¢–çŠ¶èƒƒåˆ‡é™¤æœ¯å¯¹ä»£è°¢ç»¼åˆå¾æ‚£è€ èƒƒé£Ÿç®¡åæµç—‡çŠ¶çš„å½±å“.

OBJECTIVES: To investigate the incidence of gastroesophageal reflux disease (GERD) after sleeve gastrectomy and the effect of sleeve gastrectomy in treating the symptom of gastroesophageal reflux in patients with metabolic syndrome. METHODS: We retrospectively analyzed 60 patients with metabolic syndrome who received laparoscopy sleeve gastrectomy in the Department of Bariatric and Metabolic Surgery, Third Xiangya Hospital of Central South University from April 2018 to May 2019, and assessed the changes of symptoms before and after surgery. RESULTS: The study included 31 men and 29 women. The age of these patients was 16-46 (29.17±7.23) years, ranging from 16 to 46 years. The weight and body mass index (BMI) of the patients decreased from (116.02±31.96) kg and (39.67±8.90) kg/m2 to (98.32±25.22) kg and (34.4±7.85) kg/m2 at 1 month after the surgery, respectively. The number of patients with gastroesophageal reflux was 37(61.67%) before the surgery, and 18(30.00%) at 1 month after the surgery, respectively. The number of asymptomatic patients before the surgery while had gastroesophageal reflux symptoms within 1 month after the surgery was 4(6.67%). Among the 37 patients, 6(16.62%) had persisted or worsen symptoms with gastroesophageal reflux symptoms before the surgery, 23(62.16%) had no symptoms, and 8 patients (21.62%) showed improvement of gastroesophageal reflux 1 month after the surgery. Some scores of the GERD-Health-Related Quality of Life Scale (such as reflux after dinner) were significantly lower after the surgury than those before the surgery (P<0.05). CONCLUSIONS: The symptoms of GERD are effectively improved after surgery. Sleeve gastrectomy is a feasible, safe and effective treatment for obesity with GERD.

Farnesoid X receptor interacts with cAMP response element binding protein to modulate glucagon-like peptide-1 (7-36) amide secretion by intestinal L cell.

Type II diabetes is a complex, chronic, and progressive disease. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released from the L cells which stimulate insulin secretion and promotes insulin gene expression and ß-cell growth and differentiation. Elevated levels of hormones secreted by L cells are an essential reason for diabetes improvement. GLP-1 secretion has been reported to be regulated by farnesoid X receptor (FXR), a transcriptional sensor for bile acids which also acts on glucose metabolism. Herein, we attempted to evaluate the effect of FXR on GLP-1 secretion in mouse enteroendocrine L cell line, namely STC-1, and to investigate the underlying mechanism. FXR inversely regulated GLP-1 secretion in STC-1. A total of 24 nonredundant human proteins were shown to be related to FXR by BioGRID; KEGG pathway analysis revealed that FXR was related to glucagon signaling pathway, particularly with the transcriptional activators CREB, PGC1α, Sirt1, and CBP. CREB could positively regulate GLP-1 secretion in STC-1 cells. FXR combined with CREB to inhibit its transcriptional activity, thus inhibiting proprotein convertase subtilisin/kexin type 1 protein level and GLP-1 secretion. In the present study, we demonstrated a negative regulation of GLP-1 secretion by FXR in L cell line, STC-1; FXR exerts its function in L cells through interacting with CREB, a crucial transcriptional regulator of cAMP-CREB signaling pathway, to inhibit its transcriptional activity. Targeting FXR to rescue GLP-1 secretion may be a promising strategy for type II diabetes.

Farnesoid X Receptor (FXR) Interacts with Camp Response Element Binding Protein (CREB) to Modulate Glucagon-Like Peptide-1 (7-36) Amide (GLP-1) Secretion by Intestinal L Cell.

BACKGROUND/AIMS: Type II diabetes is a complex, chronic, and progressive disease. Glucagon-like peptide-1 (7-6) amide (GLP-1) is a gut hormone released from the L cells which stimulates insulin secretion, and promotes insulin gene expression and ß-cell growth and differentiation. Elevated levels of hormone secreted by L cells are an important reason for diabetes improvement. GLP-1 secretion has been reported to be regulated by farnesoid X receptor (FXR), a transcriptional sensor for bile acids which also acts on glucose metabolism. Herein, we attempted to evaluate the effect of FXR on GLP-1 secretion in mouse enteroendocrine L cell lines, STC-1 and GLUTag, and to investigate the underlying mechanism. METHODS: ELISA and Western blot assays were employed to examine the levels of GLP-1 and FXR, and the effect of FXR on GLP-1 secretion; online database, including BioGRID and KEGG were used to identify the potential interactions between FXR and proteins and involved pathways; GST pull-down and Co-Immunoprecipitation (Co-IP) assays were performed to validate FXR-CREB interaction; Luciferase reporter gene assays were used for CREB transcriptional activity determination. RESULTS: FXR inversely regulated GLP-1 secretion in the mouse enteroendocrine L cell lines, GLUTag and STC-1. A total of 24 nonredundant human proteins were shown to be related to FXR by BioGRID; KEGG pathway analysis showed that FXR was related to glucagon signaling pathway, particularly with the transcriptional activators CREB, PGC1α, Sirt1 and CBP. CREB could positively regulate GLP-1 secretion in GLUTag and STC-1 cells. FXR combined with CREB to inhibit its transcriptional activity, thus inhibiting proprotein convertase subtilisin/ kexin type 1 (PCSK1) protein level and GLP-1 secretion. CONCLUSION: In the present study, we demonstrated a negative regulation of GLP-1 secretion by FXR in L cell lines, GLUTag and STC-1; FXR exerts its function in L cells through interacting with CREB, a crucial transcriptional regulator of cAMP-CREB signaling pathway, to inhibit its transcriptional activity. Targeting FXR to rescue GLP-1 secretion may be a promising strategy for type II diabetes.

Exendin-4 impairs the autophagic flux to induce apoptosis in pancreatic acinar AR42J cells by down-regulating LAMP-2.

This study aimed to explore the mechanism of impaired autophagy flux induced by exendin-4 and its role on cell apoptosis in pancreatic AR42J cells. The AR42J cells were treated with various concentration of exendin-4 for several time points to assess its cytotoxicity by MTT assay. Then the AR42J cells were treated by 10pM exendin-4 for 72 h, the cell death was analyzed by flow cytometry and caspase-3 level was examined by Western blot with or without the pretreatment of z-VAD-fmk to testify whether exendin-4 induces the cell apoptosis. The protein levels of LC3B, p62 and LAMP-2 were assessed by Western blot, the mRNA level of LAMP-2 was quantified by quantitative PCR in the absence or presence of LAMP-2 over-expression plasmid and the expression and activity of CatB and CatL were tested by ELISA or activity assay methods in AR42J cells treated by exendin-4. The normal rats and the diabetes-model rats by high-fat and high-sugar diet for two month then with streptozotocin intraperitoneally were subcutaneously injected with exendin-4 for 10 weeks to test the expression of LAMP-2 mRNA and protein in the pancreas. Cells pretreated with Bafilomycin A1 were detected for LC3B and p62 expressions by Western blot. Cells pretreated by 3-MA were used to assess whether 3-MA can protect from exendin-4 cytotoxicity. We found that exendin-4 can decrease the AR42J cell viability as well as increase the cell death and cleaved caspase-3 level, which all can be inhibited by z-VAD-fmk. Exendin-4 can downregulate the expression of LAMP-2 and then impair the autophagy flux to induce the accumulation of LC3B-II and p62, but cannot change the expression and activity of CatB and CatL. Bafilomycin A1 almostly have no impact on the change of LC3B and p62 protein levels induced by exendin-4. Both 3-MA and overexpressed LAMP-2 can reduce the cytotoxicity of exendin-4. Therefore, we considered the down-regulation of LAMP-2 which can impair the autophagy flux by inhibiting the fusion of autophagosomes with lysosomes to induce the AR42J cell apoptosis as the potential mechanism of chronic pancreatitis induced by exendin-4.